Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease in the United States. It encompasses both a fatty liver and nonalcoholic steatohepatitis (NASH). The NASH Clinical Research Network (NASH CRN) was established in 2002 to conduct research related to the clinical features, natural history and treatment of NAFLD in children and adults. The NASH CRN has been very productive in establishing and conducting network-wide clinical trials and numerous ancillary and pilot studies. Encouraged by its success, the NIDDK has issued RFA-DK-13-503 whose objective is to continue the NASH CRN for additional five years. The objectives of the NASH CRN during the next funding period are (a) to successfully complete three network-wide clinical trials and studies initiated during the last funding period. These include an observational longitudinal study of NAFLD in adults and children (NAFLD Database 1 and 2), a randomized double blind controlled therapeutic study of obeticholic acid in adults with NASH (FLINT, n=283), and a randomized double blind controlled therapeutic study of NAFLD in children (CyNCH, n=160). The NAFLD Database study will be amended to meet additional goals during the next funding period. These modifications may include extending the length of follow-up of those enrolled, consideration of a follow-up liver biopsy in a subset of patients without cirrhosis, adjudicated case-definition based outcomes assessment and enrolling carefully chosen controls without NAFLD for biomarker studies (b) to successfully complete a large set of pilot and ancillary studies that are ongoing, (c) to conduct additional therapeutic studies in adults and children with NASH as options currently available to treat NASH are quite limited, and (d) to initiate and complete additional ancillary studies based on extensive clinical material and biosamples collected thus far. These studies may focus on (but not limited to) natural history of NAFLD and NASH in children and adults, non-invasive assessment of disease severity (e.g., biomarker development, radiologic assessment) and disease pathogenesis (cytokine analyses, genome-wide association studies, systems biology). External expertise will be sought as needed. The NASH CRN will thus accomplish most of the NIH liver action plan for NAFLD.